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Breast/Ovarian Cancer: Lipo-Dox is administered intravenously at a dose of 50 mg/m2 once every four weeks for as long as the disease does not progress and the patient continues to tolerate treatment.
For doses <90 mg: dilute Lipo-Dox in 250 ml Dextrose 5 % in Water.
For doses >90 mg: dilute Lipo-Dox in 500 ml Dextrose 5 % in Water.
To minimize the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Lipo-Dox infusions may be administered over a 60 minute period. In the breast cancer trial program, modification of the infusion was permitted for those patients experiencing an infusion reaction as follows: 5 % of the total dose was infused slowly over the first 15 minutes. If tolerated without reaction, the infusion rate was doubled for the next 15 minutes. If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes. Subsequent Lipo-Dox infusions may be administered over a 60 minute period.
AIDS-KS patients: Lipo-Dox should be administered intravenously at 20mg/m2 every two-to-three weeks. Intervals shorter than 10 days should be avoided as drug accumulation and increased toxicity cannot be ruled out. Patients should be treated for two-to-three months to achieve a therapeutic response. Treatment should be continued as needed to maintain a therapeutic response.
Lipo-Dox, diluted in 250 ml Dextrose 5% in Water, is administered by intravenous infusion over 30 minutes.
Multiple Myeloma: Lipo-Dox is administered at 30mg/m2 on day 4 of the bortezomib 3 week regimen as 1 hour infusion administered immediately after the bortezomib infusion. The bortezomib regimen consists of 1.3mg/m2 on days 1, 4, 8, and 11 every 3 weeks. The dose should be repeated as long as patients respond satisfactorily and tolerate treatment.
For doses < 90 mg: dilute Lipo-Dox in 250 ml of 5 % (50 mg/ml) glucose solution for infusion.
For doses ≥ 90 mg: dilute Lipo-Dox in 500 ml of 5 % (50 mg/ml) glucose solution for infusion.
The intravenous catheter and tubing should be flushed with 5 % glucose solution for infusion between administration of the 2 medicinal products. Day 4 dosing of both medicinal products may be delayed up to 48 hours as medically necessary. Doses of bortezomib should be at least 72 hours apart. The first infusion of Lipo-Dox should be administered over 90 minutes, as follows: 1) 10 ml over first 10 minutes; 2) 20 ml over next 10 minutes; 3) 40 ml over next 10 minutes; 4) then, complete the infusion over a total of 90 minutes.
Subsequent doses of Lipo-Dox will be administered over 1 hour, as tolerated.
If an infusion reaction to Lipo-Dox occurs, stop the infusion and after the symptoms resolve, attempt to administer the remaining Lipo-Dox over 90 minutes, as follows: 1) 10 ml over first 10 minutes; 2) 20 ml over next 10 minutes; 3) 40 ml over next 10 minutes; 4) Then, complete the remaining infusion over a total of 90 minutes.
Infusion may be given through a peripheral vein or a central line.
All patients: If the patient experiences early symptoms or signs of infusion reaction, immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate.
DO NOT administer as a bolus injection or undiluted solution. It is recommended that the Lipo-Dox infusion line be connected through the side port of an intravenous infusion of Dextrose 5% in Water to achieve further dilution and minimize the risk of thrombosis and extravasation. The infusion may be given through a peripheral vein. Lipo-Dox must not be given by the intramuscular or subcutaneous route. Do not use with in-line filters.
To manage adverse events such as palmar-plantar erythrodysesthesia (PPE), stomatitis or hematologic toxicity, the dose may be reduced or delayed. Guidelines for Lipo-Dox dose modification secondary to these adverse effects are provided in the tables below. The toxicity grading in these tables is based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
The tables for PPE (Table 1) and stomatitis (Table 2) provide the schedule followed for dose modification in clinical trials in the treatment of breast or ovarian cancer (modification of the recommended 4 week treatment cycle): If these toxicities occur in patients with AIDS-related KS, the recommended 2 to 3 week treatment cycle can be modified in a similar manner. (see Table 1 and 2).
Click on icon to see table/diagram/image
Click on icon to see table/diagram/imageThe table for hematologic toxicity (see Table 3) provides the schedule followed for dose modification in clinical trials in the treatment of patients with breast or ovarian cancer only. Dose modification in patients with AIDS-KS is addressed in ADVERSE EFFECTS. (See Table 3.)
Click on icon to see table/diagram/imageFor multiple myeloma patients treated with Lipo-Dox in combination with bortezomib who experience PPE or stomatitis, the Lipo-Dox dose should be modified as described in Table 1 and 2 respectively.
Table 4, as follows provides the schedule followed for other dose modifications in the clinical trial in the treatment of patients with multiple myeloma receiving Lipo-Dox and bortezomib combination therapy. (See Table 4.) For more detailed information on bortezomib dosing and dosage adjustments, see the SPC for bortezomib.
Click on icon to see table/diagram/imagePatients with Impaired Hepatic Function: Base on reports, in the small amount of patients with elevated total bilirubin levels, the pharmacokinetics is similar to patients with normal total bilirubin levels. However, until further experience is gained, the pegylated liposomal doxorubicin dosage in patients with impaired hepatic function should be reduced based on the experience from the breast and ovarian cancer clinical trial programs as follows: at initiation of therapy, if the bilirubin is ranged 1.2 to 3.0 mg/dL, the first dose is reduced by 25%. If the bilirubin is more than 3.0 mg/dL, the first dose should be reduced by 50%. If the patient tolerates the first dose without an increase in serum bilirubin or liver enzymes, the dosage for cycle 2 can be increased to the next dose level, i.e., if reduced by 25% for the first dose, increase to full dose for cycle 2; if reduced by 50% for the first dose, increase to 75% of full dose for cycle 2. If the patient well tolerate, the dosage can be increased to full dose for the subsequent cycles. In the liver metastases patients with concurrent elevation of bilirubin and liver enzymes up to 4x the upper limit of the normal range, pegylated liposomal doxorubicin could be administered. Prior to pegylated liposomal doxorubicin administration, evaluate hepatic function using conventional clinical laboratory tests such as ALT/AST, alkaline phosphatase, and bilirubin is necessary.
Patients with Impaired Renal Function: As doxorubicin is metabolized by the liver and excreted in bile, dosage adjustment is not necessary. From the pharmacokinetic analysis of special population, it is confirmed that the pharmacokinetic properties are not different in the patients with the creatinine clearance between 30 - 156 mL/min. No pharmacokinetic data are available in patients with creatinine clearance of less than 30 mL/min.
AIDS-KS Patients with Splenectomy: There is no experience with pegylated liposomal doxorubicin in patients who have had splenectomy, treatment with Lipo-Dox is not recommended.
Pediatric Patients: The experience in children is limited. Lipo-Dox is not recommended in patients below 18 years of age.
Elderly Patients: Base on the Population based analysis demonstrates that age cross the range test (21-75 years) doesn't significantly alter the pharmacokinetics of pegylated liposomal doxorubicin.
